Islam Md Zohorul, Jozipovic Danica, Lopez Pablo Atienza, Krych Lukasz, Correia Banny Silva Barbosa, Bertram Hanne Christine, Hansen Axel Kornerup, Hansen Camilla Hartmann Friis
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA 02215, USA.
Microorganisms. 2024 Dec 4;12(12):2499. doi: 10.3390/microorganisms12122499.
Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of was significantly lower in the wild microbiome-associated mice, whereas was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.
实验小鼠对临床前研究至关重要，但人们严重担心，由于其免疫系统不成熟，在无特定病原体（SPF）小鼠的清洁标准化环境中饲养会导致临床前研究成果难以转化为临床应用。本研究的目的是在不受病原体影响的屋尘螨诱导的过敏性气道炎症模型中，测试野生小鼠与SPF小鼠的肠道微生物群对评估宿主免疫反应的重要性。与移植了SPF小鼠微生物群的小鼠相比，将野生小鼠微生物群移植到微生物群耗尽的小鼠体内时，可减轻肺部和血清中的组织病理学变化以及肿瘤坏死因子-α（TNF-α）。此外，与野生微生物群相关的小鼠结肠基因表达显著降低，而在回肠和结肠中均有更高的表达。肠道微生物群和代谢组学分析揭示了与野生来源微生物群相关的不同特征。因此，与SPF小鼠微生物群相比，野生小鼠微生物群可部分降低对屋尘螨诱导的过敏性气道炎症的敏感性，并且由于各自的微生物群及其衍生代谢产物对宿主免疫反应有显著影响，使用该模型的临床前研究应考虑同时使用“脏”的恢复野生状态的小鼠和SPF小鼠来测试新的治疗化合物。
